Metastatic Malignant Phyllodes Tumor Research Articles

Abstract PO4-24-08: Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy

Abstract Introduction: Phyllodes tumors (PT) are rare fibroepithelial tumors of the breast, comprising ~1% of all breast cancers, a subset of which have considerable malignant potential. Malignant phyllodes tumors (MPTs) have aggressive biological behavior and high local and distant recurrence rates. Distant metastases of MPTs have a poor prognosis given the limited treatment options available. Surgery remains the primary treatment modality for these patients; however, initial investigations suggest a potential for targeted therapies in managing this disease. The identification of targetable opportunities and a comprehensive understanding of the mutational profiles of MPTs could greatly enhance treatment options. Therefore, we aimed to assess the molecular landscape of these tumors. Methods: Phyllodes tumor samples underwent molecular profiling at Caris Life Sciences through DNA (592-gene panel or whole exome) and RNA sequencing (whole transcriptome). The MPTs were classified into primary and metastatic based on the specimen biopsy site. PD-L1+ expression was tested by IHC (SP142; ≥2+, ≥5%). Tumor mutational burden (TMB)-High was defined as ≥10 mutation/Mb. Immune cell fractions in the tumor microenvironment (TME) were estimated using quanTIseq (Finotello, 2019). Mann-Whitney U, Chi-square, and Fisher-Exact tests were applied where appropriate. Results: We identified 57 analyzed MPTs, all from female patients, with a median age of 53 years (range: 19-88). Approximately half of samples (53%, n=30) were labeled as from primary breast sites, and the remaining sites were metastatic (47%, n= 27). Of metastatic sites, lung was the most common location (74.1%, n=20/27), followed by bone, sacrum, pancreas and small bowel. Alterations in MPT include TERT promoter (56.8%, n=21/37), MED12 (51.6%, n=16/31), TP53 (40.0%, n=22/55), and NF1 (31.8%, n=14/44) mutations, with less frequent mutations of EGFR (10.5%, n=6/57), PIK3CA (7.0%, n=4/57), and BRAF (3.5%, n=2/57). As compared to primary MPT, metastatic MPT had roughly 2-fold higher prevalence of NF1 (45.5%: n=10/22 vs 18.2% n=4/22, p=0.05), KMT2D (25.9%: n=7/27 vs 10.7%: n=3/28, p=0.18), and RB1 (25.0%: n=6/24 vs 9.5%: n=2/21, p=0.25) though not significant. Multiple gene mutations were observed exclusively in lung metastases, as compared to non-lung sites including: TERT promoter (64.3%: n=9/14 vs 0.0%, p=0.08), MED12 (60.0%: n=6/10 vs 0.0%, p =0.044), and RB1 (35.3%: n=6/17 vs 0.0%, p=0.01). Conversely, NF1 (43.8%: n=7/16 vs 50.0%: n=3/6, p=1.0) and KMT2D (20.0%: n=4/20 vs 42.9%: n=3/7, p=0.32) mutation prevalence was higher in other metastatic sites. PD-L1+ expression was observed in 13.3% (n=7) of MPT overall, with similar prevalence among local and metastatic sites. No dMMR/MSI-H was observed, while low LOH (those with genomic LOH in < 16% of segment analyzed) was seen across MPT. Compared to a large cohort of breast adenocarcinoma samples (n=9,926) representing both HER2+ and HER2- tumors, MPT had low ERBB2 expression comparable to HER2- samples. B cells, M2 macrophages and neutrophils had the highest median cell fractions in the TME of MPT. Additionally, one MPT sample harbored a pathogenic NTRK1 fusion (TPM4:NTRK1), and treatment with larotrectinib for over 16 months suggests a clinical response to therapy. Conclusions: Our study demonstrates the importance of employing next generation sequencing (NGS) in MPTs to detect actionable genomic alterations. To effectively analyze fusions, an NGS panel that include RNA sequencing is recommended, considering the occurrence of NTRK1 fusion reported herein. Although HER2 transcriptional expression was low, further investigations examining HER2 IHC in PTs are still necessary. These finding therefore highlight the importance of NGS in phyllodes tumors research, as it may uncover potential targeted treatment options for patients. Citation Format: Rani Bansal, Tolulope Adeyelu, Andrew Elliott, Antoinette Tan, Jane Meisel, Matthew Oberley, Stephanie Graff, Jorge Reis-Filho, George Sledge Jr, Sarah Sammons, Laura Rosenberger. Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-24-08.

MO21-6 Efficacy and safety of chemotherapy in metastatic malignant phyllodes tumors

MO21-6 Efficacy and safety of chemotherapy in metastatic malignant phyllodes tumors

Case Report: Mitral valve obstruction by metastatic malignant phyllodes tumor

Cardiac metastases are rare. Herein, we report a case of a 37-year-old female patient with a history of borderline breast phyllodes tumor (PT) treated by surgery, admitted to our department for concomitant cardiac and pulmonary metastases of malignant PT. Cardiac metastasis occurred through direct extension from pulmonary metastasis to the left atrium via the right inferior pulmonary vein, causing severe mitral valve obstruction. Although the total surgical removal of metastases, the patient had a huge relapse of the mediastinal metastasis resulting in her death.

Metastatic Phyllodes Tumor in a Patient With Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann syndrome (BWS) is an epigenetic disorder of imprinting on the chromosome 11p15 region that presents with clinical features, such as macroglossia, abdominal wall defects, neonatal hypoglycemia, hemihypertrophy, and embryonal tumors. Phyllodes tumors (PTs) are rare fibroepithelial tumors that account for 0.3% to 1% of breast tumors and present in women aged 35 to 55 years. Here we describe a rare case of metastatic malignant phyllodes tumor in a 27-year-old woman with BWS and uniparental disomy (UPD) of chromosome 11p15.5. To our knowledge, this is the first case report in literature to describe metastatic malignant phyllodes tumor in a woman with BWS.

Apatinib treatment is effective for metastatic malignant phyllodes tumors of the breast: a case report

BackgroundWe report a rare case of malignant phyllodes tumors (MPT) with partial response to apatinib.Case presentationA 26-year-old woman had a palpable mass in her right breast for over a year. After resection, pathology indicated malignant phyllodes tumor. Eleven months after surgery, she underwent reoperation for a lung nodule, which demonstrated lung metastasis. She refused chemotherapy and was rehospitalized six months later due to leg pain. Pelvic mass biopsy revealed metastatic malignant phyllodes tumor. After concurrent chemoradiotherapy of the pelvic mass, multiple lung metastases emerged. Subsequent treatment with apatinib 500 mg/day resulted in a reduction in mass size and partial response. She survived for more than 8 months.ConclusionThe present case showed the potential therapeutic effects of apatinib in patients with MPT.

CASE REPORT: METASTATIC PHYLLODE TUMOR

Rationale: Malignant phyllodes tumors are rare breast neoplasms that are associated with a 6.2% to 25% incidence rate of distant metastasis the lung is the most common metastatic site. To date, there is no consensus regarding the treatment of metastatic malignant phyllodes breast tumors. Patient concern: A 34-year-old woman was admitted into the gynecology department for a rapidly growing left breast tumor that was first noticed month prior. Diagnosis: Core needle biopsy revealed a malignant phyllodes tumor. A chest computed tomography tomography/CT showed metastatic lymph nodes that appeared to have spread to the right axilla She was subsequently followed by course of radiotherapy, she consulted again 3 months later for a productive cough, X-ray thorax in comparison with that made preoperatively: presence of the left peri-hilar nodules which were not present on the first X-ray Interventions: A left mastectomy with axillary lymph node dissection was conducted and a thoracoabdominal flap and a split thickness skin graft were performed for the skin defect. And radiotherapie adjuvant. Lessons: As standard treatment guidelines for metastatic malignant phyllodes tumors are lacking, we opted for the aforementioned aggressive treatments that resulted in complete remission of the lung metastasis. Therefore, aggressive treatment, whenever possible, is warranted.

Metastatic recurrent malignant phyllodes in 17-year-old female

Malignant phyllodes tumor of the breast is extremely rare but what is rarer is its occurrence in adolescent girls younger than 18 years. It has a propensity for rapid growth and metastases. We present an uncommon presentation of recurrent and metastatic malignant phyllodes tumor in a 17-year-old female.

Complete remission of giant malignant phyllodes tumor with lung metastasis

Rationale:Malignant phyllodes tumors are rare breast neoplasms that are associated with a 6.2% to 25% incidence rate of distant metastasis; the lung is the most common metastatic site. To date, there is no consensus regarding the treatment of metastatic malignant phyllodes breast tumors.Patient concern:A 48-year-old woman was admitted into the breast clinic for a rapidly growing right breast tumor that was first noticed 1 month prior.Diagnosis:Core needle biopsy revealed a malignant phyllodes tumor. A chest computed tomography and positron emission tomography/CT showed metastatic lymph nodes that appeared to have spread to the right axilla, as well as multiple solitary pulmonary nodules in the right lung. Fine needle aspiration on the axillary lymph node confirmed metastasis.Interventions:A right mastectomy with axillary lymph node dissection was conducted and a thoracoabdominal flap and a split thickness skin graft were performed for the skin defect. Palliative chemotherapy with doxorubicin plus ifosfamide was performed.Outcomes:An examination conducted 3 years postsurgery showed no signs of recurrence, and the patient's overall health status was satisfactory.Lessons:As standard treatment guidelines for metastatic malignant phyllodes tumors are lacking, we opted for the aforementioned aggressive treatments that resulted in complete remission of the lung metastasis. Therefore, aggressive treatment, whenever possible, is warranted.

Malignant Phyllodes Tumor in Patient with Breast Cancer: A Case Report

Background: Phyllodes tumors (PT) have an incidence of 1 per 100,000 women and account for only 0.5% of all breast neoplasms. Herein, we present a case of malignant PT characterized by stromal overgrowth of a high-grade spindle cell sarcoma with marked stromal pleomorphism. Which this disease is rare and the lack of standard care options for it. Case Report: A 36-year-old woman with a metastatic malignant PT presented to our clinic to discuss treatment options. Immunohistochemical analysis showed that the lesion was negative for estrogen and progesterone receptor and HER-2/neu, ki67 > 80% positive and vimentin positive. During a futher evaluation in computed tomography (CT) of the chest revealed multiple lung masses was seen. Pathology review of the mastectomy product at our institution confirmed the diagnosis of a malignant PT characterized by stromal overgrowth of a high-grade spindle cell sarcoma with marked stromal pleomorphism, a high mitotic rate, and areas of necrosis. She treated with chemotherapy regimen for soft tissues sarcoma consist of vincristine, cyclophosphamide, doxorubicine. After three courses of this regimen despite of decease in severity of dyspnea the breast mass lesion progressed and the therapy change to ifosfamide and etoposide combined with Nexavar (Sorafenib). At now, the patient is treating with this policy. Conclusions: We reported a patient with malignant PT should receive adjuvant chemotherapy to reduce the risk of recurrence. We suggest chemotherapy with ifosfamide and etoposide combined with Nexavar (Sorafenib) because it is a good policy for close treatment.

Comprehensive characterization of malignant phyllodes tumor by whole genomic and proteomic analysis: biological implications for targeted therapy opportunities

BackgroundPhyllodes tumors are uncommon breast tumors that account for less than 0.5% of all breast malignancies. After metastases develop, the prognosis is poor, with very few patients living more than 1 year. The biology of this unusual cancer is not understood and, consequently, no potential targets for treatments are currently available. There has been an exponential increase in the number of commercially available tumor profiling services. Herein, we report a case of metastatic malignant phyllodes tumor for which a comprehensive molecular analysis was performed by using Clinical Laboratory Improvement Amendments (CLIA)-certified labs, providing new insights into the potential opportunities for molecularly targeted therapies for this extremely rare disease.MethodsNext-generation sequencing was performed by using the FoundationOne™ platform (Foundation Medicine, Cambridge, MA). Whole-genome array-based comparative genomic hybridization (array CGH) was performed by using the DNAarray™ (CombiMatrix Diagnostics, Irvine, CA). Immunohistochemical and morphoproteomics analysis were performed at Consultative proteomics®, The University of Texas, UT Health Medical School, Houston,TX (Robert E Brown Lab); Clarient Diagnostics, Aliso Viejo, CA; and Caris Life Sciences Target one, Irving, TX, USA.ResultsNext-generation sequencing showed 3 aberrant genes: activating mutation Q61L on NRAS; inactivating mutations Q504* and K740* on RB1; and TP53 loss. Whole-genome array-based comparative genomic hybridization (array CGH) revealed amplifications of chromosome (chr.) 1 (CKS1B gene), chr. 8 (MYC gene), and chr. 9 (CDKN2A gene) Deletions of chr. 17 (TP53), chr. 10 (GATA3), chr. 11 (FGF4 and CCND1 genes), and chr.22 (PDGFβ). Immunohistochemical analysis for relevant markers showed a positive staining for transducing-like enhancer of split (TLE) 3; secreted protein acidic and rich in cysteine (SPARC) was expressed at 2-3+ in the cytoplasm of the tumors cells, whereas mammalian target of rapamycin (mTOR) was expressed up to 2+ in the nuclei of the tumor cells.ConclusionsWe describe for the first time an NRAS mutation with concomitant activation of PI3K/Akt/mTOR in phyllodes tumor. We also found markers for sensitivity to taxane-based therapies, especially albumin-bound paclitaxel. Exploring the biology of rare malignancies by CLIA certified labs may be reasonable strategy for the development of targeted treatments.

Unusual Aggressive Breast Cancer: Metastatic Malignant Phyllodes Tumor

For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

The Efficacy of Chemotherapy against Metastatic Malignant Phyllodes Tumors of the Breast

Phyllodes tumours are rare neoplasms of the female breast. Ten-year survival of 42% is reported after surgical treatment of malignant phyllodes tumours. Metastatic tumours have a poor prognosis with no long-term survival. We present the case history of a 43 year old woman with a pulmonary metastasis from a malignant phyllodes tumour of the breast treated with chemotherapy. The role of radiation therapy and chemotherapy is not established and has not been studied in randomized trials due to the rarity of the tumor. At present, there is no consensus that patients with high-grade phyllodes tumors of the breast will benefit from either of these modalities.

Pulmonary artery obstruction due to a metastatic malignant phyllodes tumor of the breast

A 65-year-old woman with a 9-year surgical history of a left breast phyllodes tumor was admitted with progressive chest pain on effort. Computed tomography showed severe stenosis of the main pulmonary artery, with the mass originating from the ventricular septum. We planned to resect the tumor the next day. However, the next morning a pulmonary artery embolism occurred, and she developed dyspnea and lost consciousness. After carrying out cardiopulmonary resuscitation, we performed a life-saving operation. We successfully resected the huge tumor as far as possible from the right ventricle via a right atrial (RA)-tomy. However, her consciousness did not improve to better than Glasgow Coma Scale grade 7. She died from suffocation caused by metastasis invading her airway despite undergoing tracheotomy on the 77 th postoperative day.

Prise en charge des tumeurs phyllodes malignes du sein : l’expérience de l’institut Curie

Purpose Given the scarcity of malignant phyllode tumours of the breast and the absence of consensus regarding their management justify the need for institutional retrospective evaluations of clinical practices. Patients and methods Retrospective study with central pathology review of the 25 consecutive patients treated at the Institut Curie (Paris, France) between 1969 and 2006 for non metastatic malignant phyllodes tumors of the breast. The median follow-up was 65 months (7–257 months). Results Median age at diagnosis was 52 years (20–64 years). Breast surgery was conservative in five patients (20%). Surgical margins were wide (> 10 mm), narrow, involved or unknown in respectively 17 (68%), three (12%), three (12%) and two (8%) patients. Median tumour size was 65 mm (12–250 mm). Adjuvant radiotherapy was delivered in seven (28%) patients (two patients, posttumorectomy; five patients, postmastectomy) and 13 patients (52%) received anthracycline-based adjuvant chemotherapy. Five-year overall survival rate was 91% (95% CI, 80–100%). Five patients (20%) developed distant metastases (one after chemotherapy) and three (12%) locoregional relapse (one after tumorectomy and unknown margin without radiotherapy, two after mastectomy and involved margins with radiotherapy). Conclusion Wide breast surgery (that can be conservative in selected patients) is the mainstay of the treatment of non metastatic malignant phyllodes tumors of the breast. To better determine the respective roles of adjuvant systemic treatment and radiotherapy, further clinical studies and the search for new prognostic and predictive factors remain necessary.

Major response to sunitinib (Sutene®) in metastatic malignant phyllodes tumor of breast

Major response to sunitinib (Sutene®) in metastatic malignant phyllodes tumor of breast

Conservative management of breast fibroadenomas

Is it conservative or radical management to excise all fibroadenomas of the breast, especially in women less than 30 years old? Once a definite diagnosis is established by physical examination, fine-needle aspiration cytologic testing, and mammography, is it prudent to monitor women with small fibroadenomas (less than 4 cm in diameter)? We reviewed 498 cases of biopsy-proved fibroadenomas and 17 cases of phyllodes tumors (by biopsy) seen at Los Angeles County/University of Southern California Medical Center from 1986 to 1989. Analysis of patient age and measured tumor size in 203 fibroadenomas and 10 phyllodes tumor specimens revealed similar ranges for both tumors. The mean values were 28.5 years and 2.3 cm for fibroadenomas and 44 years and 3.8 cm for phyllodes tumors. No cases of coincident carcinoma within a fibroadenoma or of metastatic malignant phyllodes tumors were present in this review. As an alternative to excising all breast tumors, cytologically diagnosed fibroadenomas can be monitored, because they have no intrinsic premalignant potential and tend to regress with time. All breast tumors that rapidly increase in size should probably be excised at any age.